Pertussis
Overview
Critical pertussis (pertussis infection requiring intensive care) typically most commonly seen in young infants. In those <4 months, pertussis is often most severe and can be fatal
Elevated WBC and pulmonary hypertension are associated with increased risk of mortality. Critical Pertussis in Children (Pediatric Critical Care Medicine 2013)
Infants can present with bronchopneumonia or apnea, with paroxysmal coughing and post-tussive emesis less commonly seen
Figure 1: Typical Timeline of Pertussis Infection (from cdc.gov)
Fulminant pertussis often involves leukocytosis and pulmonary hypertension
ELSO registry review from 1992-2009 of 169 cases demonstrates a mortality rate of 69.8% for those with pertussis requiring ECMO. This increases to 83.6% mortality for those younger than 6 weeks requiring ECMO. More recent analysis (Domico et al, PCCM 2018) of infants receiving ECMO from 2002-2015 demonstrated a 72% mortality rate, with leukodepletion associated with lower rate of mortality.
WBC >100K associated with 100% mortality via conventional treatment
Risk factors associated with mortality from pertussis in multivariate models included higher WBC count, use of nitric oxide, and lower birth weight.
Pathophysiology
Leukocytosis is theorized to produce hyperviscosity and pulmonary arteriolar thrombosis, leading to pulmonary hypertension
Figure 2: Pathogenesis of Pertussis
Treatment
Isolation: Droplet precautions until 5 days of effective therapy (or three weeks after onset of symptoms in untreated patients)
Antibiotics: Macrolides are treatment of choice:
>6 months of age: Azithromycin or Clarithromycin for a 5 and 7 day course, respectively. TMP-SMX 14 day course as an alternative for those who cannot tolerate macrolide therapy
<6 months of age: Azithromycin is the recommended agent (although can be associated with hypertrophic pyloric stenosis in infants <2 weeks of age). TMP-SMX as an alternative for those >2 months and cannot tolerate macrolides (do not use in <2 months due to risk of kernicterus secondary to bilirubin displacement)
Postexposure prophyalxis for all contacts (full dosing treatment course): within 21 days of onset of cough for index case, prophylaxis can prevent development of symptoms. The American Academy of Pediatrics (AAP) recommends antimicrobial prophylaxis for all close contacts, such as child care workers or household members, regardless of their immunization status (RedBook, 2012 Report of the Committee on Infectious Diseases, 29th, Pickering LK. (Ed), American Academy of Pediatrics)
Supportive care with attention to lung protective mechanical ventilation, nutrition management, and prophylaxis
Echocardiography to evaluate for pulmonary hypertension
No clear evidence supporting use of bronchodilators, corticosteroids, Pertussis immunoglobulin
ECMO: mortality for young infants requiring ECMO is high (69.8% overall and 83.6% for infants <6 weeks) but VV ECMO may be required for refractory hypoxemia and pulmonary hypertension
Leukodepletion: via exchange transfusion or a leukofilter on an ECMO circuit, can reduce the WBC burden and presumably, the pulmonary arteriole aggregates. When compared to historical controls, leukodepletion for patients on ECMO seems to confer a survival benefit. (Rowlands, Pediatrics 2010). No clear cutoff although WBC of 50K and 30K (for patients on ECMO) has been described in infants <90 days of age. See figure below.
Figure 3: Proposed Algorithm for Leukeodepletion in Pertussis, from: Rowlands et al, Pediatrics 2010